VPS13 family proteins form conduits between the membranes of different organelles through which lipids are transferred. In humans, there are four VPS13 paralogs, and mutations in the genes encoding each of them are associated with different inherited disorders. VPS13 proteins contain multiple conserved domains. The Vps13 adaptor-binding (VAB) domain binds to adaptor proteins that recruit VPS13 to specific membrane contact sites. This work demonstrates the importance of a different domain in VPS13A function. The pleckstrin homology (PH) domain at the C-terminal region of VPS13A is required to form a complex with the XK scramblase and for the co-localization of VPS13A with XK within the cell. Alphafold modeling was used to predict an interaction surface between VPS13A and XK. Mutations in this region disrupt both complex formation and co-localization of the two proteins. Mutant VPS13A alleles found in patients with VPS13A disease truncate the PH domain. The phenotypic similarities between VPS13A disease and McLeod syndrome caused by mutations in VPS13A and XK, respectively, argue that loss of the VPS13A–XK complex is the basis of both diseases.